Extracellular matrix protein-1 secretory isoform promotes ovarian cancer through increasing alternative mRNA splicing and stemness.
Extracellular matrix protein-1 secretory isoform promotes ovarian cancer through increasing alternative mRNA splicing and stemness.
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DOI：
10.1038/s41467-021-24315-1
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发表时间：
2021-07-09
影响因子：
16.6
通讯作者：
Yang G
中科院分区：
文献类型：
--
作者：
Yin H;Wang J;Li H;Yu Y;Wang X;Lu L;Lv C;Chang B;Jin W;Guo W;Ren C;Yang G
Extracellular matrix protein-1 (ECM1) promotes tumorigenesis in multiple organs but the mechanisms associated to ECM1 isoform subtypes have yet to be clarified. We report in this study that the secretory ECM1a isoform induces tumorigenesis through the GPR motif binding to integrin αXβ2 and the activation of AKT/FAK/Rho/cytoskeleton signaling. The ATP binding cassette subfamily G member 1 (ABCG1) transduces the ECM1a-integrin αXβ2 interactive signaling to facilitate the phosphorylation of AKT/FAK/Rho/cytoskeletal molecules and to confer cancer cell cisplatin resistance through up-regulation of the CD326-mediated cell stemness. On the contrary, the non-secretory ECM1b isoform binds myosin and blocks its phosphorylation, impairing cytoskeleton-mediated signaling and tumorigenesis. Moreover, ECM1a induces the expression of the heterogeneous nuclear ribonucleoprotein L like (hnRNPLL) protein to favor the alternative mRNA splicing generating ECM1a. ECM1a, αXβ2, ABCG1 and hnRNPLL higher expression associates with poor survival, while ECM1b higher expression associates with good survival. These results highlight ECM1a, integrin αXβ2, hnRNPLL and ABCG1 as potential targets for treating cancers associated with ECM1-activated signaling. Extracellular matrix protein 1 (ECM1) has been associated with cancer but the underlying molecular mechanisms are not clear. Here, the authors show that while ECM1b isoform is a tumour suppressor, the secreted isoform ECM1a promotes tumourigenesis and chemoresistance through increasing stemness and alternative mRNA splicing in ovarian cancer.
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影响因子：
4
作者：
Humphries JD;Byron A;Humphries MJ
通讯作者：
Humphries MJ
影响因子：
5.4
作者：
Frick, C;Odermatt, A;Parkos, CA
通讯作者：
Parkos, CA
DOI：
10.1186/s13058-014-0479-6
发表时间：
2014-12-11
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
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通讯作者：
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影响因子：
29
作者：
Kennedy, MA;Barrera, GC;Edwards, PA
通讯作者：
Edwards, PA
影响因子：
4
作者：
Gómez-Contreras P;Ramiro-Díaz JM;Sierra A;Stipp C;Domann FE;Weigel RJ;Lal G
通讯作者：
Lal G